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8/17/2019 Clinical Malaria
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Clinical Malaria
Class IC2Course Tropical Medicine
Code TM
Title Professor
Lecturer Samuel McConkey
Date 2015
RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn
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Aims
• Recognise clinical signs of malaria
• Recognise signs of severe malaria
• Malaria in pregnancy
• Where do you get it?
• How to diagnose malaria
• Treatment of malaria- supportive care – How to treat severe P. falciparum
– How to treat P. vivax, ovale, malariae
– Treatment in pregnancy
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Muscular low backacheFatigue
Body-ache, myalgia, arthralgia
Headache
Fever
SweatsLethargy
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Clinical features of uncomplicated
malaria
• Minimum incubation period of 7 days
• Fever continuous or remittent
• Flu-like symptoms – Headache
– Myalgia and arthralgia
– Back ache• Tinge of jaundice
• Children stop playing, stop eating and lie
around
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Severe malaria• Cerebral malaria
• Anaemia• Metabolic acidosis
• Hypoglycaemia
• Haemoglobinuria
• Renal failure
• Juandice
• Thrombocytopenia
• Disseminated intravascular coagulopathy• Pulmonary oedema / Adult Respiratory Distress
Syndrome
Complications of malaria
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Cerebral malaria
Signs of CNS dysfunction
Seizures
Focal neurological signs
Meningeal signs
Decorticate rigidity – abnormal flexion
Decerebrate rigidity – abnormal extension
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Mechanisms of anaemia
• Lysis of parasitised erythrocytes
• Lysis of non-parasitised erythrocytes
– (immune mediated)
• Sequestration of parasitised erythrocytes
• Sequestration of iron
• Dyserythropoesis• Erythrophagocytosis
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Metabolic acidosis,
widened anion gap
• Hyperventilation
– Deep signing respiration (Kussmaul breathing)
• Negative inotropism• Impaired level of consciousness, stupor, coma
• Vomiting, abdominal pain
• K+ shift extracellularly
Treat with hydration, IV fluids and Oxygen
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Contact activated lancet
Hand-held glucose meter
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Hypoglycaemia
Classic symptoms: anxiety, sweeting,
dilation of the pupils, breathlessness,
laboured breathing, oliguria,
tachycardia, feeling of cold.
Deteriorating consciousness
Generalised convulsionsExtensor posturing
Shock and coma
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Renal failure
Oliguria and later anuriaMonitoring:
- Hourly urinary-output
- Creatinine
Treatment:
- Hydration
- Transfusion
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Thrombocytopenia
Disseminated intravascular
coagulation
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Pathogenesis of thrombocytosis in
malaria
Sequestration and destruction of platelets
Excessive removal of platelets
Platelet consumption as part of DIC
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Severe Malaria in Adults and children
Differential features
Symptoms and signs Adults Children
Cough Rare Frequent
Convulsions Common Very common
Antecendent history 5-7 days 1-2 daysResolution of coma 2.4 days 1-2 days
Neurological sequelae
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Malaria in pregnancy
non-immunes
• Severe complications: hypoglycaemia,
pulmonary oedema
• Higher mortality 2-10 fold
• Abortion, still birth, premature delivery
• Low birth weight infants
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Malaria in pregnancy
partially immunes
• Primi and secundi gravidae
• Abortion, still birth and premature labour
• Low birth weight infants• Increase in parasite rates and densities
• Placental parasitaemia
• Haemolytic anaemia
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Density of parasitaemia
Log median parasite count of 38 women
before conception 140 /mm3
Log median parasite count of 38 women
during first pregnancy 1775 /mm3
Log median parasite count of 175 non-
pregnant women 185 /mm3
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Malaria in pregnancy
Severe haemolytic anaemia in the 2nd
trimester in primipara
No deletiorious effects of quinine infusion on
uterine or foetal function
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Fried & Duffy 1996 Science 272, 1502-4
• The placenta selects for a parasite sub-
population that binds chondroitin sulphate A.
• This parasite sub-population preferentially
sequesters and multiplies int he placenta.
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Simplified regimens
Sulfadoxine-pyrimethamine once at booking
(usually in 2
nd
trimester)Repeated once at beginning of 3rd Trimester
Given with tetanus toxoid
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HIV seropositive women
• Increased prevalence of parasitaemia
• Increased density of parasitaemia
• Increased placental parasitaemia• Increased cord-blood parasitaemia
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Natural history of P. falciparum
immunity
Acquired immunity can be lost or altered by
Pregnancy
SteroidsProlonged residence in non-malarious
area
SplenectomyImmunosuppressive drugs
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Where do you get it?
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Transmission of malaria
Female Anopheles spp. – Airport malaria
Blood transfusion
Syringe passage among IVDUCongenital
Organ transplantation: heart kidneys
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Airport malaria 1966 -1999
France 26
Belgium 17
United Kingdom 14Switzerland 9
United States of America 4
Total 89
Aircraft disinfection
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Diagnosis of malaria
1. Clinical
2. Parasitological
3. Immunological
4. Molecular
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Clinical diagnosis
• High index of suspicion
• History of travel
• Great mimic
• Missdiagnosis
– Influenza
– Viral hepatitis
– Meningitis
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Immunological
Detect plasmodial LDH (Optimal),aldolase (ICT),
or histidine-rich protein-2 (ParaScreen)
Some detect P. falciparum,some P. vivax
some pan-specific
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Molecular
• PCR
• DNA hybridisation- DNA probes
General management of a
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General management of a
patient with malariaFrequent assessment of vital signs
-Early Warning Score
Artificial homeostasis, H2O, O2, H+, glucose, Na,Mg2+, Ca2+, Creatinine, BP, temperature, red
cells
Assess and treat: hydration, hypoglycaemia, hypoxia
Measure and monitor urine output e.g catheter
Daily thin film to measure parasite countConsider central venous line, arterial line
Pyrexia > 39C remove patient’s clothing, tepid sponge,fan and antipyretic
Consider other infections, cultures, lumbar puncture
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Artemisinin: arthemether:
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Artemisinin: arthemether:
artesunate
• Most rapid action - 95% clearance within
24 hours - all stages
• Cmax 1 h (oral), 5min(IV), 4-9 hours (IM)
• metabolised in liver
• half life 9 hours- (oral)
• 20-45 min (IV)
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Quinine - adverse effects
• Cinchonism on day 2 or 3
– Buzzing in ears (tinnitus)
– Dizziness
– Nausea, anorexia
– Blurred vision
• Hypoglycaemia
• Optic atrophy is rare
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Combination Therapy (ACT)
• Protects the slow acting drug
• Delays development of resistance
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P. falciparum Severe malaria
Artesunate IV or IV Quinine
And either
Doxycycline or clindamycin
• Switch to oral when tolerated
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P. falciparum non-severe malaria
Artemether + lumefantrine PO (Co-artem)
Proguanil+ atovaquone (Malarone)
Quinine PO and doxycycline or clindamycin
Mefloquine (Lariam)
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Malaria
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovalePlasmodium malariae
Plasmodium knowlesi
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Further reading
Malaria chapter by Nick White, in Manson’s
Tropical Diseases ed. Cook and Zumla
Effectiveness of antimalarial drugs Kevin
Baird NEJM April 2005 352:1565
Management of severe malaria in children
K. Maitland, A. Pollard, M. Levin. BMJ
August 2005 331:337
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Genetic factors and severe malaria
Protective
TNF alleles in promotor region
Haptoglobin phenotype
HH131 genotype
More severe
R131 allele
Genetic factors enhancing
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Genetic factors enhancing
immunity
HbS heterozygotesa thalassaemia heterozygotes
b thalassaemia heterozygotes
HbC homozygotes (93%) heterozygotes (29%)
G6PD deficiency
HLA BW 53
HLA DRB 1302
Ovalocytosis?HbE heterozygotes and homozygotes
R131 alleles
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Malaria in Ireland 2011
Plasmodium falciparum 43Plasmodium vivax 18
Deaths 1
Malaria in UK 2003
Plasmodium falciparum 1576Plasmodium vivax 322
Deaths 16